The present invention relates to apparatuses, systems and methods of treating a patient. Particularly, the present invention relates to treating medical conditions using cell therapy via body lumens. In some instances, the present invention relates to treating a blood vessel, such as in the treatment of heart disease and aneurysms.
1. Heart Disease
Heart disease continues to be a leading cause of death in the United States. The mechanism of this disease is often progressive narrowing of coronary arteries by atherosclerotic plaque which can lead to acute myocardial infarction and disabling angina. Techniques to treat coronary atherosclerosis include percutaneous transluminal coronary angioplasty, (or PTCA, commonly referred to as balloon angioplasty), atherectomy, and coronary stenting. In each of these treatments, compression of the plaque and expansion of the coronary artery, or removal of the atherosclerotic plaque, often restores lumen patency. In stenting, a stent, such as a metal or wire cage-like structure, is expanded and deployed against the plaque.
Despite the overall initial success of these procedures, many patients undergoing these therapeutic procedures to clear blocked coronary arteries will suffer restenosis (re-blockage) at some point after the initial procedure. Such restenosis may be a manifestation of the general wound healing response or may be due to a variety of other factors.
Thus, it would be desired to provide devices, systems and methods which would provide therapeutic benefits to injured or diseased tissue. Such benefits may include reduction of the incidence of restenosis, particularly in blood vessels treated for atherosclerosis. However such benefits may be applicable to any body lumen which suffers from occlusion and possible restenosis. In addition, such benefits may include a reduction in any initial injury induced by intervention, such as by stenting. At least some of these objectives will be met by the embodiments of the present invention.
2. Aneurysms
An aneurysm is the focal abnormal dilation of a blood vessel. The complications which arise from aneurysms can include rupture, embolization, fistularisation and symptoms related to pressure on surrounding structures. Aneurysms are commonly found in the abdominal aorta, being that part of the aorta which extends from the diaphragm to the point at which the aorta bifurcates into the common iliac arteries. These abdominal aortic aneurysms typically occur between the point at which the renal arteries branch from the aorta and the bifurcation of the aorta. When left untreated, an abdominal aortic aneurysm may eventually cause rupture of the aorta with ensuing fatal hemorrhaging in a very short time. High mortality associated with the rupture has led to the development of transabdominal surgical repair of abdominal aortic aneurysms.
A clinical approach to aneurysm repair which is less invasive than conventional transabdominal surgery is known as endovascular grafting. Endovascular grafting typically involves the transluminal placement of a prosthetic arterial graft within the lumen of the artery. The graft may be attached to the internal surface of an arterial wall by means of attachment devices (often similar to expandable stents), one above the aneurysm and a second below the aneurysm. Such attachment devices permit fixation of a graft to the internal surface of an arterial wall without sewing.
It would be desirable, to provide devices, systems and methods that improve the treatment of aneurysms, such as improving fixation of the graft, increased resistance to graft migration and leakage and/or improvements in the characteristics of the surrounding tissue once in place. At least some of these objectives will be met by the embodiments of the present invention.
3. Use of Cell-Based Therapies
Methods have been developed for using pluripotent stem cells for therapeutic applications, including the delivery of therapeutic genes. Pluripotent stem cells appear to have the ability to differentiate into a number of different cell types, including neurons, cardiomyocytes, skeletal muscle, smooth muscle and pancreatic beta cells, to name a few, that are involved in the pathogenesis of many human diseases, such as atherosclerosis, diabetes, hypertension and various others. However, current methods have limitations which preclude the successful use of such pluripotent stem cells in treating various medical conditions.
To begin, a stem cell per se exhibits almost no target tissue selectivity. As such, if stem cells are simply introduced to target tissues by current methods, such as intravenously or by direct injection, a safety concern is the risk that the cells will differentiate into a non-target cell type and disrupt the normal functions in the target tissues. At worst, this may result in tumorigenesis and/or patient mortality. A possible solution is to use stem cells which have been triggered to becoming the target cell type, i.e. progenitor cell types such as smooth muscle progenitor cells. Since these stem-cell derived progenitor cells have started onto the differentiation pathway sufficiently to be “committed” to becoming the desired cell type, there is reduced risk of tumorigenesis or differentiation into an undesired cell type. The drawback to this approach (i.e. the use of progenitor cells) is that the engraftment efficiency is usually inversely related to the extent of cell differentiation. Thus, while the use of stem-cell-derived progenitor cells may reduce or eliminate safety concerns, the fact that the progenitor cells are further down the differentiation pathway as compared to pluripotent stem cells means that their engraftment efficiency is reduced, and this will in turn reduce the likelihood of a clinical benefit.
Alternatively, differentiated somatic cells have been used for cell-based therapies. However, these applications have also been limited by the lack of methods to provide efficient engraftment as described above.
Thus, it would be desirable to provide devices, systems and methods that will deliver therapeutic cells directly to the target site, such that regardless of the extent to which these cells have differentiated, their engraftment into the target site will be significantly improved. At least some of these objectives will be met by the embodiments of the present invention.
4. Immune Issues Related to Use of Non-Autologous Cells
Interest has developed in using non-autologous cells for cell-based therapies, particularly non-autologous embryonic stem cells. Embryonic stem cells may have properties, such as pluripotentiality and infinite replicative life span, that are not obtainable with autologous somatic stem cells. In addition, various non-human cells may be used in the treatment of human diseases, for example, porcine pancreatic beta cells for treatment of diabetes. However, non-autologous and non-human cells are attacked by the patient's immune system, thus limiting their long term efficacy and viability.
Thus, it would be desirable to provide devices, systems and methods that allow the delivery of non-autologous cells to a desired tissue site while simultaneously isolating them from the patient's immune system. This would reduce or prevent any immunologic rejection of the cells. At least some of these objectives will be met by the embodiments of the present invention.